Enteric neurons are interconnected to generate positive and negative feedback circuits. Positive feedback generates so called network behaviour, i.e. a slow buildup of coordinated activity in large populations of neurons. The hypothesis behind the project is that appropriate activation of enteric neural networks is a critical feature of innate immunity, at several levels: activation of secretory neuron networks leads to secretion of chloride from the intestinal crypts, which carries with it water, mucus, secretory IgA and possibly defensins from Paneth cells located at the bottom of the crypts. We also have evidence for neurally mediated stimulation of intestinal stem cell activity. These hypotheses are tested in in vitro and in vivo animal systems, and in humans. We have access to mucosal biopsies taken during endoscopies and to perfusion techniques which inable us to collect relevant samples from patients with e.g. inflammatory bowel disease and the irritable bowel syndrome.
Another idea that we will pursue is that enteric network activation may act as an “adjuvant” in the more long-term mucosal immunity response. This possibility is particularly relevant in Crohn´s disease, which leads to a transmural inflammation. If this idea is correct, pharmacological intervention with enteric network activity may be used to improve the efficiency of oral mucosal vaccines.
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Kordasti S, Sjövall H, Lundgren O, and Svensson L. (2004). Serotonin and vasoactive intestinal peptide antagonists attenuate rotavirus diarrhoea. Gut 53: 952-957.
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